Childhood neoplasm

Summary

Childhood neoplasm (MONDO:0021079) is a cancer (an umbrella term covering 14 Mondo subtypes) with 10 cohort genes (8 CIViC-evidence somatic drivers; 10 ClinVar predisposition records) and 11 clinical trials. Top therapeutic interventions include sugammadex, fluoride ion f-18, and f-18.

At a glance

• Classification: Cancer
• Umbrella term: 14 Mondo subtypes
• Cohort genes: 10
• ClinVar variants: 10
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood neoplasm
Mondo ID	MONDO:0021079
NCIT	C6283
UMLS	C1368871
MedGen	237153
Is cancer (heuristic)	yes

Also known as: childhood neoplasm · childhood neoplasm (disease) · childhood tumor · childhood tumour · neoplasm (disease) of childhood · paediatric neoplasm · paediatric neoplasm (disease) · paediatric tumour · pediatric neoplasm · pediatric neoplasm (disease) · pediatric tumor

Data availability: 10 ClinVar variants.

Disease family

An umbrella term covering 14 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › childhood neoplasm

Related subtypes (47): pre-malignant neoplasm, endocrine gland neoplasm, giant cell tumor, hematopoietic and lymphoid system neoplasm, skin neoplasm, mesenchymal cell neoplasm, epidural spinal canal neoplasm, skeletal muscle neoplasm, trophoblastic neoplasm, cancer, germ cell tumor, benign neoplasm, upper aerodigestive tract neoplasm, histiocytoma, embryonal neoplasm, head and neck neoplasm, epithelial neoplasm, reproductive system neoplasm, non-seminomatous lesion, odontogenic cyst, phosphaturic mesenchymal tumor, thyroglossal duct cyst, hamartoma, mesenchymoma, mesothelial neoplasm, peritoneal neoplasm, virus associated tumor, nail tumor, respiratory tract neoplasm, spindle cell neoplasm, mixed neoplasm, urinary system neoplasm, cystic neoplasm, melanocytic neoplasm, digestive system neoplasm, nervous system neoplasm, neoplasm of thorax, connective tissue neoplasm, bronchial adenomas/carcinoids childhood, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, erythroplakia, retroperitoneal neoplasm, cardiovascular neoplasm, dermoid or epidermoid cyst of the central nervous system, connective and soft tissue neoplasm, NTRK fusion positive cancer, RET fusion positive cancer

Subtypes (14): childhood astrocytic tumor, childhood spinal cord tumor, childhood kidney neoplasm, childhood infratentorial neoplasm, pediatric meningioma, childhood mediastinal neurogenic neoplasm, childhood ependymoma, childhood germ cell tumor, childhood optic nerve glioma, childhood malignant neoplasm, childhood carcinoid tumor, childhood choroid plexus neoplasm, childhood testicular neoplasm, childhood adrenal gland pheochromocytoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
142114	NM_007194.4(CHEK2):c.591del (p.Val198fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2578510	NM_004456.5(EZH2):c.1891del (p.Ile631fs)	EZH2	Likely pathogenic	criteria provided, single submitter
2578509	NM_003072.5(SMARCA4):c.1420-1G>T	SMARCA4	Likely pathogenic	criteria provided, single submitter
361658	NM_000127.3(EXT1):c.1066G>A (p.Val356Ile)	EXT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
89653	NM_000249.4(MLH1):c.1153C>T (p.Arg385Cys)	MLH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
232581	NM_058216.3(RAD51C):c.52C>T (p.Pro18Ser)	RAD51C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
185334	NM_000051.4(ATM):c.6776C>G (p.Ser2259Cys)	C11orf65	Uncertain significance	criteria provided, multiple submitters, no conflicts
639463	NM_002878.4(RAD51D):c.917A>G (p.Gln306Arg)	RAD51D	Uncertain significance	criteria provided, multiple submitters, no conflicts
539668	NM_004168.4(SDHA):c.1324G>A (p.Ala442Thr)	SDHA	Uncertain significance	criteria provided, multiple submitters, no conflicts
573206	NM_000455.5(STK11):c.1179C>G (p.Asn393Lys)	STK11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 26 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SDHA	Act	CHRCC,HCC,LGGNOS	CIViC #5176
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
CHEK2	Act	BRCA	CIViC #8950
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63
MLH1			CIViC #3532
RAD51C			CIViC #4762
RAD51D			CIViC #4765

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDHA	Orphanet:139411	Carney triad
SDHA	Orphanet:154	Familial isolated dilated cardiomyopathy
SDHA	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHA	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHA	Orphanet:44890	Gastrointestinal stromal tumor
SDHA	Orphanet:97286	Carney-Stratakis syndrome
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
STK11	Orphanet:2869	Peutz-Jeghers syndrome
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma
EXT1	Orphanet:321	Multiple osteochondromas
EXT1	Orphanet:502	Trichorhinophalangeal syndrome type 2
EXT1	Orphanet:55880	Chondrosarcoma
EZH2	Orphanet:3447	Weaver syndrome
MLH1	Orphanet:144	Lynch syndrome
MLH1	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
RAD51C	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD51C	Orphanet:84	Fanconi anemia
RAD51D	Orphanet:1331	Familial prostate cancer
RAD51D	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
C11orf65	HGNC:28519	ENSG00000166323	Q8NCR3	Protein MFI	clinvar
EXT1	HGNC:3512	ENSG00000182197	Q16394	Exostosin-1	clinvar
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	clinvar
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	clinvar
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDHA	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
C11orf65	Protein MFI	Acts as an inhibitor of mitochondrial fission.
EXT1	Exostosin-1	Glycosyltransferase forming with EXT2 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
RAD51C	DNA repair protein RAD51 homolog 3	Essential for the homologous recombination (HR) pathway of DNA repair.
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 6 · Druggable fraction: 0.4

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	5.5×	0.145
Enzyme (other)	2	2.4×	0.301
Other/Unknown	6	1.1×	0.526

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
C11orf65	Other/Unknown	no
EXT1	Enzyme (other)	yes	2.4.1.224	Exostosin, GT64_dom, Nucleotide-diphossugar_trans
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
RAD51C	Other/Unknown	no		Rad51_C, DNA_recomb/repair_RecA-like, RecA_ATP-bd
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like

Expression context

Cohort genes with no expression data: 0.

9 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right testis	3
ganglionic eminence	2
left testis	2
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	2
sperm	2
apex of heart	1
heart left ventricle	1
mucosa of transverse colon	1
cervix squamous epithelium	1
cortical plate	1
hindlimb stylopod muscle	1
lower esophagus mucosa	1
descending thoracic aorta	1
saphenous vein	1
stromal cell of endometrium	1
embryo	1
ventricular zone	1
deltoid	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
C11orf65	163	ubiquitous	marker	sperm, left testis, right testis
EXT1	285	ubiquitous	marker	stromal cell of endometrium, saphenous vein, descending thoracic aorta
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
RAD51C	281	ubiquitous	marker	primordial germ cell in gonad, right testis, male germ line stem cell (sensu Vertebrata) in testis
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EZH2	9,646
SMARCA4	8,138
SDHA	6,141
STK11	5,146
CHEK2	4,795
MLH1	4,435
RAD51C	3,396
RAD51D	3,089
EXT1	1,449
C11orf65	312

Intra-cohort edges

A	B	Sources
CHEK2	RAD51D	string_interaction
MLH1	RAD51D	string_interaction
RAD51C	RAD51D	biogrid_interaction, intact, string_interaction

Structural data

PDB: 9 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHEK2	O96017	38
EZH2	Q15910	38
SMARCA4	P51532	31
RAD51C	O43502	17
RAD51D	O75771	17
MLH1	P40692	7
EXT1	Q16394	6
SDHA	P31040	5
STK11	Q15831	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C11orf65	Q8NCR3	74.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 89. Enrichment computed across 10 evidence-associated genes (9 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	2	101.5×	0.004	RAD51C, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	94.0×	0.004	RAD51C, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	94.0×	0.004	RAD51C, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	94.0×	0.004	RAD51C, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	87.5×	0.004	RAD51C, RAD51D
Homologous DNA Pairing and Strand Exchange	2	84.6×	0.004	RAD51C, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	2	66.8×	0.005	RAD51C, RAD51D
Presynaptic phase of homologous DNA pairing and strand exchange	2	60.4×	0.005	RAD51C, RAD51D
HDR through Homologous Recombination (HRR)	2	42.3×	0.009	RAD51C, RAD51D
TP53 Regulates Transcription of DNA Repair Genes	2	40.3×	0.009	MLH1, RAD51D
Defective Mismatch Repair Associated With MLH1	1	634.4×	0.012	MLH1
Defective Mismatch Repair Associated With PMS2	1	634.4×	0.012	MLH1
Meiotic recombination	2	28.8×	0.014	MLH1, RAD51C
Negative Regulation of CDH1 Gene Transcription	2	26.7×	0.015	SMARCA4, EZH2
Regulation of TP53 Activity through Phosphorylation	2	26.2×	0.015	STK11, CHEK2
Mismatch Repair	1	317.2×	0.016	MLH1
Diseases of Mismatch Repair (MMR)	1	317.2×	0.016	MLH1
AMPK inhibits chREBP transcriptional activation activity	1	158.6×	0.029	STK11
RNA Polymerase II Transcription	3	7.5×	0.029	SMARCA4, STK11, MLH1
Transcriptional Regulation by TP53	2	13.8×	0.038	STK11, MLH1
Defective EXT2 causes exostoses 2	1	90.6×	0.040	EXT1
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	90.6×	0.040	EXT1
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	90.6×	0.040	MLH1
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	90.6×	0.040	MLH1
Stabilization of p53	1	84.6×	0.040	CHEK2
Gene expression (Transcription)	3	6.0×	0.040	SMARCA4, STK11, MLH1
FOXO-mediated transcription of cell death genes	1	79.3×	0.040	STK11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	1	74.6×	0.040	CHEK2
Formation of the non-canonical BAF (ncBAF) complex	1	74.6×	0.040	SMARCA4
Formation of the canonical BAF (cBAF) complex	1	70.5×	0.040	SMARCA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
telomere maintenance via recombination	2	306.4×	0.003	RAD51C, RAD51D
G1 to G0 transition	2	280.9×	0.003	STK11, EZH2
meiotic DNA recombinase assembly	1	1685.2×	0.010	RAD51C
hypersensitivity	1	1685.2×	0.010	EXT1
heart field specification	1	1685.2×	0.010	EXT1
female meiosis sister chromatid cohesion	1	1685.2×	0.010	RAD51C
lymphocyte adhesion to endothelial cell of high endothelial venule	1	1685.2×	0.010	EXT1
meiotic metaphase I homologous chromosome alignment	1	1685.2×	0.010	MLH1
smoothened signaling pathway involved in lung development	1	1685.2×	0.010	EXT1
sweat gland development	1	1685.2×	0.010	EXT1
perichondral bone morphogenesis	1	1685.2×	0.010	EXT1
positive regulation of vesicle transport along microtubule	1	1685.2×	0.010	STK11
reciprocal meiotic recombination	2	112.3×	0.010	RAD51C, RAD51D
regulation of signal transduction by p53 class mediator	2	76.6×	0.010	STK11, CHEK2
intrinsic apoptotic signaling pathway in response to DNA damage	2	64.8×	0.010	CHEK2, MLH1
heterochromatin formation	2	51.1×	0.011	SMARCA4, EZH2
protein catabolic process	2	47.5×	0.012	CHEK2, EXT1
hepatocyte homeostasis	1	842.6×	0.014	EZH2
meiotic spindle midzone assembly	1	842.6×	0.014	MLH1
stomach development	1	842.6×	0.014	EXT1
mesenchymal cell differentiation involved in bone development	1	842.6×	0.014	EXT1
response to leukemia inhibitory factor	1	842.6×	0.014	EXT1
male meiosis chromosome segregation	1	561.7×	0.014	MLH1
regulation of gliogenesis	1	561.7×	0.014	EZH2
cellular response to trichostatin A	1	561.7×	0.014	EZH2
fluid transport	1	561.7×	0.014	EXT1
negative regulation of mitotic recombination	1	561.7×	0.014	MLH1
developmental growth involved in morphogenesis	1	561.7×	0.014	EXT1
response to heparin	1	561.7×	0.014	EXT1
positive regulation of glucose mediated signaling pathway	1	561.7×	0.014	SMARCA4

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 5

Druggability breadth: 5 of 10 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SDHA	LINEZOLID
STK11	FEDRATINIB
CHEK2	NERATINIB
EZH2	TAZEMETOSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHEK2	30	4
STK11	17	4
EZH2	6	4
SMARCA4	2	2
SDHA	1	4
C11orf65	0	0
EXT1	0	0
MLH1	0	0
RAD51C	0	0
RAD51D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LINEZOLID	4	SDHA
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	CHEK2, STK11
MIDOSTAURIN	4	STK11
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
GEFITINIB	4	CHEK2
TAZEMETOSTAT	4	EZH2
DINACICLIB	3	STK11
DOVITINIB	3	CHEK2, STK11
LESTAURTINIB	3	CHEK2, STK11
RUBOXISTAURIN	3	CHEK2, STK11
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4
AZD-1480	2	STK11
SU-014813	2	CHEK2, STK11
R-406	2	STK11
TOZASERTIB	2	STK11
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2
DEFOSBARASERTIB	2	CHEK2
PREXASERTIB	2	CHEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EZH2	839	Binding:833, Functional:6
CHEK2	690	Binding:687, Functional:2, ADMET:1
STK11	244	Binding:244
SMARCA4	230	Binding:207, ADMET:12, Functional:11
SDHA	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK11	2.7.11.1	non-specific serine/threonine protein kinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
EXT1	2.4.1.224, 2.4.1.225	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase, N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SMARCA4	230
STK11	244
CHEK2	690
EZH2	839

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
LINEZOLID	4	SDHA
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	CHEK2, STK11
MIDOSTAURIN	4	STK11
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
GEFITINIB	4	CHEK2
TAZEMETOSTAT	4	EZH2
DINACICLIB	3	STK11
DOVITINIB	3	CHEK2, STK11
LESTAURTINIB	3	CHEK2, STK11
RUBOXISTAURIN	3	CHEK2, STK11
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4
AZD-1480	2	STK11
SU-014813	2	CHEK2, STK11
R-406	2	STK11
TOZASERTIB	2	STK11
DORAMAPIMOD	2	CHEK2
FORETINIB	2	CHEK2
CENISERTIB	2	CHEK2
ILORASERTIB	2	CHEK2
CEP-11981	2	CHEK2
DEFOSBARASERTIB	2	CHEK2
PREXASERTIB	2	CHEK2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	SDHA, STK11, CHEK2, EZH2
B	Phased (≥1) drug, not yet approved	1	SMARCA4
C	Druggable family + PDB, no drug	1	EXT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	C11orf65, MLH1, RAD51C, RAD51D

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
C11orf65	0	—
EXT1	0	—
MLH1	0	—
RAD51C	0	—
RAD51D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE4	1
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03107325	PHASE4	WITHDRAWN	Biokinetics Study for F-18 FDG in Pediatric Molecular Imaging
NCT03728543	PHASE2/PHASE3	UNKNOWN	the Efficacy and Safety of Sugammadex in Children 0-2 Years Old
NCT05887882	PHASE1	SUSPENDED	Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors
NCT04471961	Not specified	ACTIVE_NOT_RECRUITING	Analyse of Tumour and Constitutional DNA for the Study of the Determinism in Child Neoplasia
NCT05592132	Not specified	RECRUITING	Use of Virtual Reality in Pain Management in Pediatric Oncology
NCT06584877	Not specified	ENROLLING_BY_INVITATION	Investigating How Childhood Tumours and Congenital Disease Develop
NCT07315230	Not specified	NOT_YET_RECRUITING	Pediatric Midline Post Fossa Tumors Prognostic Factors and Outcomes
NCT07378423	Not specified	RECRUITING	Questionnaire on Congenital Cancer Signs Through Self-Assessment
NCT01838564	Not specified	COMPLETED	The PediQUEST Study: Evaluation of Pediatric Quality of Life and Evaluation of Symptoms Technology
NCT02847130	Not specified	COMPLETED	Identifying, Understanding, and Overcoming Barriers to the Use of Clinical Practice Guidelines in Pediatric Oncology
NCT04856020	Not specified	UNKNOWN	Role of Gray Scale and Color Doppler Ultrasound in Diagnosis of Pediatric Neck Masses

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUGAMMADEX	4	1
FLUORIDE ION F-18	3	1
F-18	0	1